Regular, daily bowel movements are helpful, even essential, in maintaining a good appetite, an overall sense of well-being, good energy levels, and a positive attitude. They also can aid in prevention of various gastrological conditions developing. However, constipation (meaning fewer than three passing of stools per week or of hard and dry stools, which cause a bloated feeling and possible painful hemorrhoids) is a common health concern in the general population, especially the elderly. Left untreated, constipation may induce abdominal pains, weight gain, and psychological distress. According to the National Institute of Diabetes and Kidney Diseases (NIDDK, 2010), 63 million US adults suffer from chronic constipation. Children under the age of 15 are the second most afflicted group. Thus, presently there is a huge market need for regularity-directed supplements and safe, everyday use, over--the-counter (OTC) medications. (A. Elizabeth Sloan; Neutraceuticals World; “Sloan Trends,” May 2012, pp. 16-17).
Over the centuries, numerous, palliative, naturally occurring or man-made synthetic chemical remedies have been available to induce bowel movement or to loosen the stool and treat constipation. Many of these agents are available as over-the-counter (OTC) remedies to consumers. Like most remedies, however, there is wide variation in their effectiveness and individual preferences for each class of laxatives. For example, popular natural fibers, and bulk-forming agents such as psyllium seed husks [sold as Metamucil® (trademark of Procter & Gamble Company), Benefiber® (trademark of Novartis AG)], guar gum, bran and others, exert their effect by bulking up the stool by retaining more water; therefore these agents must be consumed with plenty of water. However, these agents are not immediately effective, can require a person to take up to 3 doses per day, and are tiresome to consume in large amounts of water. Also, in some individuals, these agents simply do not work. Another fiber product is FiberChoice® (trademark of GlaxoSmithKline), a chewable tablet form, containing a moderate amount (4 g) of a vegetable derived fiber, inulin.
U.S. Pat. No. 7,977,319 claims an ultra-thigh fiber supplement made with guar, oat, psyllium, locust bean gum, pectin, and vitamins for weight loss and better cardiovascular health.
The chemical stimulant laxatives, which work on the intestinal mucosa, are based on the active chemical structural motifs of anthraquinone [e.g., cascara, buckthorn, aloe vera, and senna extract sold as Senokot® (trademark of Purdue Frederick Company)], or triphenylmethane (e.g., bisacodyl) or a stool softener, such as sodium docusate, a surfactant, sold as Dulcolax® (trademark of Boehringer Ingelheim). These chemical stimulant laxatives are used when gentler, natural laxatives have not worked over several days, such as can happen during travel in different time zones affecting circadian rhythms or consuming foods that are not customary for that person and possibly more difficult to digest, and next day relief is needed. However, these agents are not recommended for chronic use and should be used with care or as directed by a physician because they can have serious side-effects. See, for example, an article by Joo J., et al., “Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited”, J. Clin. Gastroenterology 26(4), 283-6 (1998).
Another popular OTC laxative is based on the use of the chemical polyethylene glycol, or PEG-3350, sold as SoftLax, MiraLAX® (trademark of MSD Consumer Care, Inc.) or GlycoLax® (trademark of Kremers Urban Development Co.). These products work as an osmotic laxative, by drawing water into the colon thereby promoting bowel movement. This laxative will usually cause a bowel movement in one to three days, and may be taken for a short term, up to 7 days, for relief of chronic constipation.
One home remedy that is long recognized for its gentle, reliable, fast acting laxative effect is prunes, which are hot air dried plums. Prunes are remarkable in that they will not spoil or rot even for years stored at room temperature in open air, due to their having a very high antioxidative potential. Daily consumption at breakfast of 6-7 oz, of prune juice (extract), available in most US grocery stores, is reliably effective in promoting same day bowel movement and has been shown safe even when used for decades. There are no known side-effects.
Alternatively, one may consume 8-10 dry prunes or soft moist pitted prunes with breakfast, an unwelcome chewing exercise as they are often tough to chew and have a gummy mouth feel. These are available in portable pouches in various sizes.
The mechanism of action of the laxative effect of prunes is not known. Prunes contain the sugar alcohol sorbitol, a non-stimulant laxative, and the natural laxative dihydrophenyl isatin (see Vivek Kumar, et al., Clinical Geriatrics, April 2007, pp. 37-42), and about 6% or 0.06 g of dietary fiber per g of prunes. Sorbitol, a hyperosmotic agent, causes the intestines to flood with water, softening the stools and promoting bowl movement.
Various improved formulations of prunes have been proposed. US Application 20030012862, published Jan. 16, 2003, proposes encapsulating prune powder from pulverized prunes. However, the proposed dose of 750 mg of prune powder in capsules falls far short of any known effective dose.
Another highly advertised product is Prunelax® (trademark of Laboratorios Garden House Farmaceutica S.A.) administered as a tablet (dose 2-3, tablets at bedtime) or capsule (dose 4-6 capsules at bedtime). Each tablet contains a small amount (125 mg) of dried prune extract, 960 mg of powdered senna leaves and 180 mg of powdered senna pods derived from the leaves and pods of the senna plant (S. Alexandrina or S. Angustifolia). The active ingredient of senna is the same anthraquinone derivatives as mentioned above as their dimeric glycosides A and B, in the chemical stimulant category as noted above (Merck Index, XIII Edition; 8528, 8529). Despite the name, the prune content of these tablets or capsules is almost negligible to have a significant contributory laxative effect.
A free flowing granular prune powder, containing a small amount of calcium stearate, is available from Mayan Sun Co. in Washington State. The powder is prepared by further drying of prunes and then pulverizing into a powder. It is ˜80% by weight of prunes. Adding and stirring 47.5 g of this powder (equivalent ˜10 prunes) in 175 mL of warm water makes a very thick suspension with a bitter taste. It is unsuitable for the desired application.
U.S. Pat. No. 5,573,232 claims a prune formulation having an ingestible syrup for softening the stool and improving regularity of elimination by mixing 1-10% by volume of psyllium powder in prune concentrate (actually a prune puree from whole prunes) at the point of ingestion. It forms into a very thick syrup and is unsuitable and unappetizing for the purpose.
US Patent Application 20110135758 claims a process for producing a laxative containing a mixture of prune juice, magnesium, magnesium hydroxide and purified water. Magnesium hydroxide has laxative properties (see Merck Index). However, mixing metallic magnesium with prune juice is not understood as to its purpose.
The use of dietary supplements is currently a popular multibillion dollar US market for products such as quick energy drinks with nearly 50 brands available, e.g. 5-hour Energy® (trademark of Living Essentials, LLC), which combines in water, megadoses of water soluble B-vitamins, amino acids, and caffeine in a ˜2 oz bottle. These products do not provide a laxative that can taste pleasant with these ingredients.
Clearly, a safe, reliable, pleasant tasting formulation for use as a laxative or as a regularity-directed supplement in adults and teens that can be used repeatedly over long periods of time is needed.